A placebo-controlled crossover study of iloperidone augmentation for residual anger and irritability in major depressive disorder.

Academic Article


  • BACKGROUND: Even when patients experience remission with antidepressants, many continue to report anger attacks and excessive irritability despite continued treatment. Iloperidone antagonizes 5-HT-2a, D2, and alpha-1 receptors, which can have anti-aggressive effects. We examined iloperidone's safety and efficacy as an augmentation agent in outpatients with partially remitted major depressive disorder (MDD) with residual symptoms of anger and irritability. METHODS: A total of 13 outpatients with partially remitted MDD [currently treated with selective serotonin reuptake inhibitors (SSRIs)] received four weeks of iloperidone or placebo, followed by one week of washout. Patients were then crossed over to the other treatment arm for 4 weeks. Treatment arms were randomized and double blind; and two sites were used for the study. Analyses compared treatment response using the Symptom Questionnaire (SQ) Anger/Hostility Subscale as the primary outcome measure. RESULTS: There was no significant differential effect of iloperidone × weeks on the SQ Anger/Hostility Subscore over the course of the study, compared with placebo × weeks, regardless of administration order (p = 0.77). CONCLUSIONS: Iloperidone did not significantly outperform placebo on measures of anger or irritability in patients with partially remitted MDD and residual anger/irritability.
  • Authors


  • anger, augmentation, iloperidone, irritability, major depressive disorder
  • Digital Object Identifier (doi)

    Author List

  • Ionescu DF; Fava M; Kim DJH; Baer L; Shelton RC; Cusin C
  • Start Page

  • 4
  • End Page

  • 12
  • Volume

  • 6
  • Issue

  • 1